Summary: 1) Vascular Stiffness as a Risk Factor: The importance of vascular stiffness as a risk factor has been confirmed in populations from the HEALTH ABC and BLSA studies. Associations have been found between PWV and gait speed (among HEALTH ABC participants with peripheral arterial disease, each standard deviation higher in PWV was independently associated with 0.028 m/s slower gait speed at baseline and throughout the study period (P < 0.01)(Watson 2011)), a decline in muscle mass (Abbatecola 2011), and longitudinal rise in blood pressure (Najjar 2008). Furthermore, central blood pressure has been shown to predict all cause and cardiovascular mortality (Wang 2010). These findings underlie the importance of the ongoing VALIDATE study which will assess the factors leading to unhealthy vascular aging as measured by PWV, intimal medial thickness, coronary calcium scoring, among other tests, when completed in the near future. 2) Longitudinal Vascular Stiffness Data: Repeated measures in subjects from the BLSA and SardiNIA studies have enabled longitudinal analysis of data spanning over 25 years and 10 years, respectively. Importantly, data across the multiple eras of measurement have recently been corrected to account for multiple testers and equipment, thereby expanding the pool of data for analysis. While these analyses are ongoing, data from the VALIDATE study have also enabled researchers to improve the assessment of vascular parameters by MRI (Hoi 2011) and improve PWV assessment. Longitudinal data has now been analyzed and manuscripts concerning these findings, which will enable construction of interventional trials, are now in preparation. 3) Causes of Vascular Stiffening: Analysis now includes genetic as well as various epidemiologic factors. Data obtained from participants in the SardiNIA Study have revealed the importance of Col4A1 gene (Tarasov 2009) and a second genetic element located in a desert region of the genome (Mitchell 2012), findings which has been confirmed in replication studies and larger Consortia-based analysis. As well, environmental factors such as Vitamin D (Giallauria 2011) and interactions with components of the metabolic syndrome including obesity (Scuteri 2011) have been found to play important roles in arterial stiffening. In addition, advanced glycation endproducts AGEs (represented by the specific AGE serum carboxymethyl-lysine (CML)) elevated AGEs have been shown to be associated with increased arterial stiffness, a known predictor of adverse cardiovascular outcomes, among relatively healthy community-dwelling adults. Interventions to lower levels of AGEs, such as altering the pattern of dietary intake, warrant examination as putative novel strategies to lower arterial stiffness in adults (Am J Hypertens. 2009 Jan;22(1):74-9).